Composite particle, method for producing the same, dispersion solution, magnetic biosensing apparatus and magnetic biosensing method

Abstract

To provide a method for producing composite particles small in particle size, excellent in mono-dispersibility, high in magnetic-substance content per particle, large in saturation magnetization, excellent in dispersion stability and having non-specific adsorption suppressibility. The method includes (1) mixing a first liquid and particles to prepare a mixture solution;(2) mixing the mixture solution and a second liquid to prepare an emulsion containing a dispersoid formed of the first liquid and the particles; (3) mixing a polymer compound with the emulsion; and (4) fractionating the emulsion to extract the first liquid from the dispersoid to produce the composite particles each containing the particles and the polymer compound, characterized in that the dispersoid has a single-peak particle size distribution and a dispersity index (Dhw/Dhn) calculated from a number-average hydrodynamic particle size (Dhn) and a weight-average hydrodynamic particle size (Dhw) is 1.5 or less.

1 . A method for producing composite particles comprising:
 (1) mixing a first liquid and particles to prepare a mixture solution;   (2) mixing the mixture solution and a second liquid to prepare an emulsion containing a dispersoid formed of the first liquid and the particles;   (3) mixing a polymer compound with the emulsion; and   (4) fractionating the emulsion to extract the first liquid from the dispersoid to produce the composite particles each containing the particles and the polymer compound, wherein the dispersoid has a single-peak particle size distribution and a dispersity index (Dhw/Dhn) calculated from a number-average hydrodynamic particle size (Dhn) and a weight-average hydrodynamic particle size (Dhw) is 1.5 or less.   
     
     
         2 . The method for producing composite particles according to  claim 1 , wherein the emulsion is a mini-emulsion. 
     
     
         3 . The method for producing composite particles according to  claim 1 , wherein the first liquid is an organic solvent insoluble in the second liquid or a monomer. 
     
     
         4 . The method for producing composite particles according to  claim 1 , wherein the polymer compound varies between an insoluble state and a soluble state depending upon the pH of the second liquid. 
     
     
         5 . The method for producing composite particles according to  claim 1 , further comprising changing a pH of the emulsion from a pH at which the polymer compound is soluble in the second liquid to a pH at which the polymer compound is insoluble. 
     
     
         6 . The method for producing composite particles according to  claim 1 , wherein the polymer compound is an amphoteric polymer compound having a hydrophobic site and a hydrophilic site. 
     
     
         7 . The method for producing composite particles according to  claim 1 , wherein the particles are particles containing a magnetic substance and a weight-average dry particle size (Dw) of the magnetic substance is 20 nm or less. 
     
     
         8 . Composite particles each having a structure in which substantially spherical multinuclear particles formed of a plurality of magnetic substances are surrounded by a film-state polymer compound, wherein a polydispersity index (Dw/Dn) calculated from a number-average dry particle size (Dn) and a weight-average dry particle size (Dw) of the composite particles is 1.2 or less; the weight-average dry particle size (Dw) of the composite particles falls within a range of 50 nm to 300 nm; a content of the magnetic substances in the composite particles is not less than 50 wt % to not more than 90 wt %; and a weight-average dry particle size (Dw) of the substantially spherical multinuclear particles formed of the magnetic substances is 20 nm or less. 
     
     
         9 . The composite particles according to  claim 8 , wherein the composite particles at least partly have a hollow structure. 
     
     
         10 . A dispersion solution prepared by dispersing composite particles in water or an aqueous solution, wherein the dispersion solution has a single-peak particle size distribution and a dispersity index (Dhw/Dhn) calculated from a number-average hydrodynamic particle size (Dhn) and a weight-average hydrodynamic particle size (Dhw) is 1.2 or less; the composite particles each have a structure in which substantially spherical multinuclear particles formed of a plurality of magnetic substances are surrounded by a film-state polymer compound; a polydispersity index (Dw/Dn) calculated from a number-average dry particle size (Dn) and a weight-average dry particle size (Dw) of the composite particles is 1.2 or less; the weight-average dry particle size (Dw) of the composite particles falls within a range of 50 nm to 300 nm; a content of the magnetic substances in the composite particles is not less than 50 wt % to not more than 90 wt %; and a weight-average dry particle size (Dw) of the substantially spherical multinuclear particles formed of the magnetic substances is 20 nm or less. 
     
     
         11 . A magnetic biosensing apparatus having the composite particles A according to  claim 8  and a magnetic sensor. 
     
     
         12 . A magnetic biosensing method comprising binding a target substance trapping substance to a surface of the composite particles A according to  claim 8  to obtain composite particles B capable of trapping the target substance; bringing the composite particles B capable of trapping the target substance into contact with a sample to trap the target substance in the sample; and
 detecting the composite particles B trapping the target substance by the magnetic sensor to determine the presence/absence or concentration of the target substance in the sample. 
 
     
     
         13 . The magnetic biosensing method according to  claim 12 , comprising fixing the composite particles B trapping the target substance to the surface of the magnetic sensor and applying a static magnetic field to the composite particles B fixed on the surface of the magnetic sensor.